Jung-der Wang - Profile on Academia.edu (original) (raw)
Papers by Jung-der Wang
Journal of Occupational Health, 2016
Archives of Toxicology, Aug 1, 2003
Vinyl chloride monomer (VCM) is a known human carcinogen, which may be metabolized by cytochrome ... more Vinyl chloride monomer (VCM) is a known human carcinogen, which may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2), and glutathione S-transferase T1 (GSTT1). A DNA-repair gene, X-ray repair cross-complementing group 1 (XRCC1, exon 10), may also be implicated in the process of VCM-related carcinogenesis. Thus, VCM-exposed workers with inherited susceptible metabolic and DNA-repair genotypes may experience an increased risk of genotoxiciy. This study was designed to investigate whether metabolic and DNA-repair genotypes affected sister chromatid exchange (SCE) frequency in occupationally VCM-exposed workers from polyvinyl chloride (PVC) manufacturing plants. Study subjects comprised 61 male workers having experienced VCM exposure, and 29 male controls. Questionnaires were administered to obtain detailed histories of cigarette-smoking habits, alcohol consumption behavior, and occupation. The frequency of SCE in peripheral lymphocytes was determined using a standardized method, and genotypes of CYP2E1, ALDH2, GSTT1 and XRCC1 were identified by the polymerase chain reaction (PCR) procedure. Our results demonstrated that smoking, age and VCM exposure and XRCC1 (P=0.03), CYP2E1 (P=0.04), and ALDH2 (P=0.08) were significantly associated with an increased SCE frequency. Further analysis of gene combinations, including CYP2E1, ALDH2 and XRCC1, revealed an increased trend for these genotypes to influence SCE frequencies for the low VCM-exposure group (P<0.01), but not so for the high VCM-exposure group (P=0.29) or for controls (P=0.49). These results suggest that workers with susceptible metabolic and DNA-repair genotypes, may experience an increased risk of DNA damage elicited by VCM exposure. Keywords Vinyl chloride monomer AE CYP2E1 AE ALDH2 AE XRCC1 AE Sister chromatid exchange
Human and Ecological Risk Assessment, May 1, 2002
The use of molecular biomarkers in epidemiologic studies has been advanced as a way to improve ri... more The use of molecular biomarkers in epidemiologic studies has been advanced as a way to improve risk assessments for occupational and environmental exposures to toxic agents. We have used the detection of two cancer-related, molecular biomarkers of vinyl chloride exposure (mutant ras-p21 and mutant p53) to examine workers with equivalent cumulative exposures that would be above or below the current permissible workplace exposure limit for vinyl chloride for differences in the presence of these biomarkers. Workers with cumulative exposures above the current permissible exposure limit (equivalent of > 40 ppm-years) have a statistically significantly increased occurrence of both biomarkers in comparison to unexposed controls (p < 10 -3 ). Although workers with cumulative exposures of < 10 ppm-years, i.e., well below the current limit, do not have a statistically significantly increased occurrence of these biomarkers (p > 0.05), workers with cumulative exposures of 10 to 40 ppm-years, i.e., still below the current limit, are found to have a statistically significant increase (p < 0.05). This suggests that the current exposure limit may not be adequately protective and illustrates the potential utility of molecular biomarkers in the refinement of risk assessments for toxic exposures.
PubMed, Jun 12, 2010
Background: Expected years of life lost (EYLL) in dialysis patients are rarely discussed. This st... more Background: Expected years of life lost (EYLL) in dialysis patients are rarely discussed. This study compared life expectancy, EYLL and survival between hemodialysis (HD) and peritoneal dialysis (PD) patients. Methods: Adults who underwent maintenance dialysis at National Taiwan University Hospital from 1995 to 2006 were followed up until December 2007. Kaplan-Meier analysis and a constant excess hazard model were used to estimate and project long-term survival. EYLL was calculated by subtracting the life expectancy of patients from that of age- and sex-matched referents. HD patients were then matched with PD patients on age, sex and diabetes mellitus (DM). Life expectancy, EYLL and survival between the 2 groups were compared. Mortality risks were determined by the Cox model. Results: Before matching, the 305 HD patients were older than the 428 PD patients (62.4 ± 13.7 vs. 53.1 ± 16.7 years; p<0.0001). More HD patients had DM (HD vs. PD, 29.2% vs. 20.6%; p=0.0072). Life expectancy and EYLL of HD patients were 8.8 and 11.5 years, compared with those of PD patients (19.9 and 7.4 years). After matching, life expectancy (p=0.790) and EYLL (p=0.793) of both groups (236 patients each) were similar. Age (adjusted hazard ratio [AHR] = 1.07; 95% confidence interval [95% CI], 1.05-1.09) and DM (AHR=3.81; 95% CI, 2.28-6.36) were independent mortality predictors. For diabetic patients who underwent HD, a better survival rate was observed (AHR=0.24; 95% CI, 0.11-0.53). Conclusions: After matching, HD and PD patients had similar life expectancy and EYLL. Survival was better for diabetic patients if they received HD.
Occupational health in Taiwan
PubMed, May 25, 2002
Challenges facing a developing country during transition to newly developed status include lack o... more Challenges facing a developing country during transition to newly developed status include lack of: a hazard communication system, a prudent industrial zoning policy, and occupational safety and health (OSH) technology and personnel. The authors offer an approach to the future that encompasses implementation of a pollution prevention system, comprehensive coverage of occupational injuries and diseases, and integration of information technology with OSH protection.
Health and Quality of Life Outcomes, Nov 14, 2016
Background: Gastroesophageal reflux disease (GERD) has become a major health problem globally, af... more Background: Gastroesophageal reflux disease (GERD) has become a major health problem globally, affecting patients' health-related quality of life (HRQOL). Barrett's esophagus (BE) is a precancerous lesion associated with GERD. BE patients might not only suffer from HRQOL losses by GERD but also face psychological distress due to the increased risk of developing cancer. However, the majority of patients in Asia have shorter BE segment which is different from the West. This study aimed to determine whether the HRQOL in BE patients were worse than in healthy referents in Taiwan. Methods: Patients who received referral esophagogastroduodenoscopy for various symptoms were evaluated for the existence of BE. Lesions were judged as endoscopically suspected esophageal metaplasia (ESEM) if they showed morphological resemblances to BE by endoscopy. The diagnosis of BE was confirmed by histology with intestinal metaplasia or gastric metaplasia based on the Montreal definition. The World Health Organization Quality of Life (WHOQOL-BREF) was administered to BE patients before treatment. For each BE patient, we selected 2 age-, sex-, educational background and municipality-matched healthy referents, sampled by simple randomization method from a national survey in Taiwan. Multiple linear regression models were constructed to control the potential confounders. Results: A total of 84 patients diagnosed with BE were enrolled as BE group and then compared with 168 healthy referents. The BE group had significantly lower WHOQOL-BREF scores than those of healthy referents in the physical domain (P < 0.05) but higher scores in the environment domain (P < 0.05). In the physical domain, the BE group had significantly lower scores in various facets, including pain, discomfort, sleep and rest and dependence on medications or treatments. There was no significant difference in social and psychological domains between the BE group and healthy referents. Conclusions: BE patients suffer from poor sleep and rest and high dependence on medications, which significantly reduce their quality of life. Individual facets of each domain warrants a better clinical healthcare to improve quality of life of BE patients.
PubMed, May 1, 2002
Mutant p53 protein and anti-p53 antibody in circulating blood can be detectedamong individuals wi... more Mutant p53 protein and anti-p53 antibody in circulating blood can be detectedamong individuals with mutations of the p53 tumor suppressor gene. Plasma mutant p53 protein and anti-p53 antibody have also been associated with vinyl chloride monomer (VCM) exposure, although the mechanism of VCM-related carcinogenesis remains unclear. Polymorphisms of metabolic and DNA repair genes have been implicated in chemical exposure-related carcinogenesis. The aim of this study is to explore the association between polymorphisms of metabolic and DNA repair genes with mutant p53 protein and anti-p53 antibody expression induced by VCM. Study subjects comprised 333 male workers occupationally exposed to VCM. Plasma mutant p53 protein and anti-p53 antibody detected with ELISA were grouped together as p53 overexpression. Genotypes of cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2), glutathione S-transferase T1 (GSTT1), and X-ray repair cross-complementing group 1 (XRCC1, exon 10) genes were identified by the PCR. High VCM exposure group had significantly higher p53 overexpression as compared with low exposure group [odds ratio (OR), 2.1; 95% confidence interval (CI), 1.1-3.8]. Individuals having experienced a high VCM exposure and displaying a XRCC1 Gln-Gln genotype had a highest risk of p53 overexpression among those having different combinations of VCM exposure and XRCC1 genotypes (OR, 6.5; 95% CI, 1.7-24.2). Interestingly, those subjects reflecting a CYP2E1 c2c2 genotype among the low VCM-exposure group demonstrated a greater risk of p53 overexpression (OR, 9.8; 95% CI, 1.2-81.6) as compared with those experiencing a low VCM exposure and CYP2E1 c1c1/c1c2 genotypes. Additional analysis revealed that individuals possessing more susceptible XRCC1 Gln-Gln, CYP2E1 c2c2, ALDH2 1-2/2-2, and non-null GSTT1 genotypes were more likely to reveal p53 overexpression. Our results suggest that susceptible XRCC1 and CYP2E1 genotypes may modulate the mutation of the p53 gene among VCM-exposed workers.
Toxicology Letters, May 1, 1995
Vinyl chloride monomer (VCM) is a suspected human carcinogen. Its metabolite, chloroethylene epox... more Vinyl chloride monomer (VCM) is a suspected human carcinogen. Its metabolite, chloroethylene epoxide, is able to alkylate the DNA molecule and to produce single strand breakage (SSB). A total of 244 workers from 4 polyvinyl chloride (PVC) manufacturing factories were recruited to assess the SSB of their peripheral lymphocyte DNA. The method of alkaline unwinding and hydroxyapatite chromatography was used to detect and calculate frequencies of SSB. In addition, h'epatitis B and C markers and the liver function of the workers were also examined. The worker's cumulative exposures to VCM were retrospectively constructed from the current monitoring data and each worker's job history. Multiple linear regression models were constructed to predict the worker's level of SSB and liver functions based on various exposure indices and variables, such as age, sex, smoking, drinking, and hepatitis markers. The results showed that current smoking and drinking status, and the presence of VCM exposures on the previous day were 3 major determinants of the level of SSB. Among the liver function tests, only y-glutamyl transpeptidase (GGT) was associated with current VCM exposures. In contrast, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were mainly affected by the presence of hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (anti-HCV). We conclude that GGT should be considered to be included in the regular health screening of VCM workers, and that the SSB method may not be suitable for long-term monitoring of cumulative exposure because of the quick DNA repair mechanism in humans. Keywor&: Single strand breakage (SSB); Peripheral lymphocyte; Alkaline unwinding and hydroxyapatite chromatography; Gamma glutamyl transpeptidase (GGT); Time-weighted average (TWA)
Journal of Occupational and Environmental Medicine, Jun 1, 2006
• Compare epidermal nerve density (END), estimated by immunohistochemical staining of skin biopsi... more • Compare epidermal nerve density (END), estimated by immunohistochemical staining of skin biopsies from the distal forearm, in ten men exposed occupationally to hand-transmitted vibrations and in age-and gendermatched control subjects. • Identify the results of sensory threshold testing and nerve conduction studies, and any correlations found between these or other factors on the one hand and END on the other. • Explain the implications of these findings for the development and early diagnosis of hand-arm vibration syndrome.
Toxicology, Sep 1, 2007
Although a relationship between vinyl chloride monomer (VCM) and liver cirrhosis has been reporte... more Although a relationship between vinyl chloride monomer (VCM) and liver cirrhosis has been reported, the underlying mechanisms are not clear. Cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2) and glutathione S-transferase theta 1 (GSTT1) enzymes are involved in activation and detoxification of VCM, and thus may be important determinants of interindividual susceptibility to VCM-induced liver damage, including liver cirrhosis. The objective of this study was to evaluate if metabolizing genetic polymorphisms could modify individual susceptibility to liver fibrosis of the VCM exposure. CYP2E1, ALDH2, and GSTT1 polymorphisms were determined by the PCR-RFLP method among 320 workers who were employed in five polyvinyl chloride manufacturing plants. Cumulative VCM exposure levels for study subjects were calculated using a job exposure matrix model. Thirteen workers were diagnosed as having liver fibrosis by using ultrasonography. We observed a dose-response trend between VCM exposure and liver fibrosis. Regarding the results on genetic polymorphisms, CYP2E1 c2c2 genotype showed a significant increase in the risk of liver fibrosis as compared to those with CYP2E1 c1c1 or c1c2 genotypes. No differences were observed between GSTT1 and ALDH2 genotypes and liver fibrosis. In summary, our result suggests that genetic polymorphism in CYP2E1 may be responsible for individual differences in susceptibility to liver fibrosis with regard to chronic VCM exposure. Thus, polymorphism analysis of metabolizing enzymes might be useful in the risk assessment of liver damage in workers with VCM exposure.
Journal of Occupational and Environmental Medicine, Sep 1, 2004
Occupational and Environmental Medicine, Jun 1, 1995
Objectives-To evaluate the effects of chronic exposure to lead on the peripheral nervous system i... more Objectives-To evaluate the effects of chronic exposure to lead on the peripheral nervous system in lead workers. Methods-Nerve conduction velocity and electromyographic studies were per- formed on 31 lead workers of a battery recycling factory and 31 sex and age matched controls. 25 cases with mild dis- tal extensor weakness of the upper limbs were classified as the lead neuropathy subgroup and the rest of the lead workers as the lead exposure subgroup. Blood lead concentrations and haematological and biochemical data were recorded. An index of cumulative exposure to lead was calculated by the summation of multiply- ing the average blood concentration of lead with the duration of exposure at various jobs. Results-Compared with the control group, the distal motor latency of the median nerve was significantly prolonged in the lead neuropathy subgroup, but not in the exposure subgroup. Only six of 31 workers had nerve conduction abnormalities, whereas electromyographic evi- dence of denervation was found in 93.5% of the lead neuropathy subgroup and 83-5% in the lead exposure subgroup. The electromyographic abnormalities found were neurogenic polyphasic waves in all 29 workers with abnormal electromyo- graphic findings (grade +++ in seven cases and grade ++ in the rest). Spontaneous activity was only recorded in seven workers, with grade + in four and grade ++ in three. There was a positive linear correlation between the index of cumulative exposure to lead and the distal motor latencies of the tibial nerve as well as a negative correlation with con- duction velocities of the sural nerve after multivariate analysis and control of potential confounding by age and sex. No correlation could be found between the electrophysiological values and a simple duration of exposure or concentration of blood lead. A non-parametric analysis showed that there was a trend of higher index of cumulative exposure to lead with more severe electromyographic changes. Electromyographic abnormality also occurred in workers with blood lead con- centrations between 17-4 and 58 ug/dI. Conclusion-Electromyographic study in the distal extensors of the upper limbs may be used as a tool for biological moni- toring of effect in lead workers.
Journal of Occupational and Environmental Medicine, Apr 1, 2003
• Identify previously reported findings relating occupational vinyl chloride monomer (VCM) exposu... more • Identify previously reported findings relating occupational vinyl chloride monomer (VCM) exposure to liver disease. • Relate how -and to what extent -hepatitis B surface antigen (HBsAg) status and particular job-related tasks interact to increase the risk of hepatocellular carcinoma in workers exposed to VCM. • Explain postulated mechanisms by which hepatitis B virus infection and VCM exposure may interact to cause liver cancer.
Quality of Life Research, May 24, 2008
Aims To compare the psychometric properties of the World Health Organization Quality of Life-BREF... more Aims To compare the psychometric properties of the World Health Organization Quality of Life-BREF (WHO-QOL-BREF) instrument and the St. George's Respiratory Questionnaire (SGRQ), and to examine the association between pulmonary function and domains and items of these questionnaires in patients with chronic obstructive pulmonary disease (COPD). Methods The WHOQOL-BREF and the SGRQ were administered to 211 patients. The reliability and validity of, and correlations among, the domain scores were examined. Multiple regression analyses were performed to identify which items were independently associated with subjects' lung functions. Results Both questionnaires showed good internal consistency (a [ 0.8), except the SGRQ symptoms domain (a = 0.66), minimal ceiling and floor effects, and good item convergent and item discriminant validity. There were moderate correlations between physical domain of the WHOQOL-BREF and activity, impacts and total domains of the SGRQ, and between psychological domain of the WHOQOL-BREF and impacts and total domains of the SGRQ. Eighteen items were significantly associated with lung function, particularly those items relating to mobility/ walking and activities of daily living (ADL). Conclusion Both the WHOQOL-BREF and the SGRQ showed comparable reliability and validity. Items related to mobility/walking and ADL may be useful in clinical screening for lung function impairment.
Occupational and Environmental Medicine, Aug 1, 1998
Objectives-Risk factors for increased blood lead concentration (BPb) has been investigated. Howev... more Objectives-Risk factors for increased blood lead concentration (BPb) has been investigated. However, the eVect of sibship and Chinese herbal medicine on BPb has not been systematically studied. In this study BPb data from voluntary testing was used to determine if Chinese herbal medicine and sibship were associated with BPb. Methods-319 children aged 1-7 were tested for BPb. Meanwhile, parents were interviewed to obtain information including consumption of Chinese herbal medicine, living environment, lifestyle, and sibship of the children tested. Results-The mean (SD) BPb of 319 preschool children was 4.4 (2.4) µg/dl. The consumption of Ba-baw-san (a Chinese herbal medicine) was significantly associated with increased BPb in children (p=0.038). Further multivariate regression analysis of BPb in 50 pairs of siblings showed the factors of being brothers explained 75% of variation for BPb, and being sisters and brother-sister explained 51% and 41% of variation respectively. Conclusion-Chinese herbal medicine and children's play patterns within the family expressed in diVerent types of sibship are the main determinants of low concentrations of BPb in preschool children of Taiwan.
Preventive medicine reports, Dec 1, 2016
This study estimates the annual numbers of eight work-related cancers, total losses of quality-ad... more This study estimates the annual numbers of eight work-related cancers, total losses of quality-adjusted life years (QALYs), and lifetime healthcare expenditures that possibly could be saved by improving occupational health in Taiwan. Three databases were interlinked: the Taiwan Cancer Registry, the National Mortality Registry, and the National Health Insurance Research Database. Annual numbers of work-related cancers were estimated based on attributable fractions (AFs) abstracted from a literature review. The survival functions for eight cancers were estimated and extrapolated to lifetime using a semi-parametric method. A convenience sample of 8846 measurements of patients' quality of life with EQ-5D was collected for utility values and multiplied by survival functions to estimate quality-adjusted life expectancies (QALEs). The loss-of-QALE was obtained by subtracting the QALE of cancer from age-and sex-matched referents simulated from national vital statistics. The lifetime healthcare expenditures were estimated by multiplying the survival probability with mean monthly costs paid by the National Health Insurance for cancer diagnosis and treatment and summing this for the expected lifetime. A total of 3010 males and 726 females with eight work-related cancers were estimated in 2010. Among them, lung cancer ranked first in terms of QALY loss, with an annual total loss-of-QALE of 28,463 QALYs and total lifetime healthcare expenditures of US$36.6 million. Successful prevention of eight work-related cancers would not only avoid the occurrence of 3736 cases of cancer, but would also save more than US$70 million in healthcare costs and 46,750 QALYs for the Taiwan society in 2010.
Cancer Detection and Prevention, 2003
Aims: To determine the presence of Asp13-p21-ki-ras oncoprotein and p53 oncoprotein in the plasma... more Aims: To determine the presence of Asp13-p21-ki-ras oncoprotein and p53 oncoprotein in the plasma of vinyl chloride monomer (VCM)-workers in Taiwan. Methods: We used enhanced chemiluminescence (ECL) western blotting to detect Asp13-p21-ki-ras and ELISA to detect mutant p53 protein (p53-Ag) and anti-p53 antibodies (p53-Ab) in the plasma of VCM-exposed workers. Results: Twenty-five out of 251 (10%) VCM-workers were positive for Asp13-p21-ki-ras in plasma, but 0 out of 36 controls were positive. There were 15 out of 95 (15.8%) plasma-positives among the more highly exposed (>480 ppm-month) workers and 10 out of 156 (6.4%) plasma-positives among the lesser exposed (≤480 ppm-month). Compared to the unexposed controls, age and drinking adjusted odds ratios (95% CI) were 1.2 (0.1, 9.8) in the lower exposed workers, and 4.8 (0.8, 28) in the higher exposed workers, and there was a significant linear trend between exposure and plasma positivity (P = 0.001). Thirty-three out of 251 (13.2%) VCM-workers were positive for the p53 over-expression (10% with positive p53-Ag and 2.8% with positive p53-Ab). There was a significant association between cumulative VCM exposure concentration and positive p53 expression (P = 0.032) among VCM-workers after adjusting for age, hepatitis, drinking and smoking status. Conclusions: Asp13-p21-ki-ras oncoprotein and p53 over-expression (p53-Ag or p53-Ab) can be found in the plasma of VCM-workers in Taiwan, and a significant dose-response relationship exists between plasma oncoproteins expression and VCM exposure.
Analysis of outpatient visits at a university hospital occupational and environmental clinic between 1987 and 1995
Chinese Journal of Public Health, 1999
Cluster Analysis of Environmental and Electromagnetic Field Health Risk Perception in Taiwan
Environmental health perspectives, Sep 13, 2011
P004 Recognition and compensation schemes for asbestos-related diseases (ards) in selected east asian countries
Introduction Asbestos products have been manufactured and consumed in large quantities in many Ea... more Introduction Asbestos products have been manufactured and consumed in large quantities in many East Asian countries over the past few decades. However, relatively few asbestos-related diseases (ARDs) have been recognised and compensated. This study compared the recognition and compensation schemes for ARDs in Japan, South Korea, Hong Kong and Taiwan. Methods Published materials were reviewed, followed with interviews with key informants. We first reviewed the conditions of asbestos exposures and compared the compensation statistics of ARDs across the studied regions. Secondly, we examined the legal frameworks for the recognition and compensation for ARDs, including the designs of compensation policies, sources of fund, eligibility for compensation, types of diseases and recognition criteria, and the scopes and levels of compensation benefits. Results In Japan, South Korea and Hong Kong, confirmed ARDs can be compensated regardless of claimants’ employment status, either through workers’ compensation insurance scheme or through compensation scheme under relief acts specifically designed for asbestos related health damages. In 2011, Japan, South Korea and Hong Kong compensated 1922, 632 and 18 ARD cases, respectively. In contrast, there have been very few ARDs being recognised in Taiwan (0 case in 2011), where compensation is restricted to workers with occupational asbestos exposure and thresholds for filing workers’ compensation are relatively high. Discussions Low recognition of ARDs can be attributed to biomedical factors, which involve the difficulties in making precise diagnosis, lack of information on previous exposure dose and duration, difficulties in establishing causality due to long disease latency and contamination from confounding exposures. Nevertheless, social factors are also important in determining how the social burden of occupational disease is negotiated. Among all, the design and function of workers’ compensation system, including policy frameworks and mechanisms for the recognition of occupational diseases, play an essential role.
Journal of Occupational Health, 2016
Archives of Toxicology, Aug 1, 2003
Vinyl chloride monomer (VCM) is a known human carcinogen, which may be metabolized by cytochrome ... more Vinyl chloride monomer (VCM) is a known human carcinogen, which may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2), and glutathione S-transferase T1 (GSTT1). A DNA-repair gene, X-ray repair cross-complementing group 1 (XRCC1, exon 10), may also be implicated in the process of VCM-related carcinogenesis. Thus, VCM-exposed workers with inherited susceptible metabolic and DNA-repair genotypes may experience an increased risk of genotoxiciy. This study was designed to investigate whether metabolic and DNA-repair genotypes affected sister chromatid exchange (SCE) frequency in occupationally VCM-exposed workers from polyvinyl chloride (PVC) manufacturing plants. Study subjects comprised 61 male workers having experienced VCM exposure, and 29 male controls. Questionnaires were administered to obtain detailed histories of cigarette-smoking habits, alcohol consumption behavior, and occupation. The frequency of SCE in peripheral lymphocytes was determined using a standardized method, and genotypes of CYP2E1, ALDH2, GSTT1 and XRCC1 were identified by the polymerase chain reaction (PCR) procedure. Our results demonstrated that smoking, age and VCM exposure and XRCC1 (P=0.03), CYP2E1 (P=0.04), and ALDH2 (P=0.08) were significantly associated with an increased SCE frequency. Further analysis of gene combinations, including CYP2E1, ALDH2 and XRCC1, revealed an increased trend for these genotypes to influence SCE frequencies for the low VCM-exposure group (P<0.01), but not so for the high VCM-exposure group (P=0.29) or for controls (P=0.49). These results suggest that workers with susceptible metabolic and DNA-repair genotypes, may experience an increased risk of DNA damage elicited by VCM exposure. Keywords Vinyl chloride monomer AE CYP2E1 AE ALDH2 AE XRCC1 AE Sister chromatid exchange
Human and Ecological Risk Assessment, May 1, 2002
The use of molecular biomarkers in epidemiologic studies has been advanced as a way to improve ri... more The use of molecular biomarkers in epidemiologic studies has been advanced as a way to improve risk assessments for occupational and environmental exposures to toxic agents. We have used the detection of two cancer-related, molecular biomarkers of vinyl chloride exposure (mutant ras-p21 and mutant p53) to examine workers with equivalent cumulative exposures that would be above or below the current permissible workplace exposure limit for vinyl chloride for differences in the presence of these biomarkers. Workers with cumulative exposures above the current permissible exposure limit (equivalent of > 40 ppm-years) have a statistically significantly increased occurrence of both biomarkers in comparison to unexposed controls (p < 10 -3 ). Although workers with cumulative exposures of < 10 ppm-years, i.e., well below the current limit, do not have a statistically significantly increased occurrence of these biomarkers (p > 0.05), workers with cumulative exposures of 10 to 40 ppm-years, i.e., still below the current limit, are found to have a statistically significant increase (p < 0.05). This suggests that the current exposure limit may not be adequately protective and illustrates the potential utility of molecular biomarkers in the refinement of risk assessments for toxic exposures.
PubMed, Jun 12, 2010
Background: Expected years of life lost (EYLL) in dialysis patients are rarely discussed. This st... more Background: Expected years of life lost (EYLL) in dialysis patients are rarely discussed. This study compared life expectancy, EYLL and survival between hemodialysis (HD) and peritoneal dialysis (PD) patients. Methods: Adults who underwent maintenance dialysis at National Taiwan University Hospital from 1995 to 2006 were followed up until December 2007. Kaplan-Meier analysis and a constant excess hazard model were used to estimate and project long-term survival. EYLL was calculated by subtracting the life expectancy of patients from that of age- and sex-matched referents. HD patients were then matched with PD patients on age, sex and diabetes mellitus (DM). Life expectancy, EYLL and survival between the 2 groups were compared. Mortality risks were determined by the Cox model. Results: Before matching, the 305 HD patients were older than the 428 PD patients (62.4 ± 13.7 vs. 53.1 ± 16.7 years; p<0.0001). More HD patients had DM (HD vs. PD, 29.2% vs. 20.6%; p=0.0072). Life expectancy and EYLL of HD patients were 8.8 and 11.5 years, compared with those of PD patients (19.9 and 7.4 years). After matching, life expectancy (p=0.790) and EYLL (p=0.793) of both groups (236 patients each) were similar. Age (adjusted hazard ratio [AHR] = 1.07; 95% confidence interval [95% CI], 1.05-1.09) and DM (AHR=3.81; 95% CI, 2.28-6.36) were independent mortality predictors. For diabetic patients who underwent HD, a better survival rate was observed (AHR=0.24; 95% CI, 0.11-0.53). Conclusions: After matching, HD and PD patients had similar life expectancy and EYLL. Survival was better for diabetic patients if they received HD.
Occupational health in Taiwan
PubMed, May 25, 2002
Challenges facing a developing country during transition to newly developed status include lack o... more Challenges facing a developing country during transition to newly developed status include lack of: a hazard communication system, a prudent industrial zoning policy, and occupational safety and health (OSH) technology and personnel. The authors offer an approach to the future that encompasses implementation of a pollution prevention system, comprehensive coverage of occupational injuries and diseases, and integration of information technology with OSH protection.
Health and Quality of Life Outcomes, Nov 14, 2016
Background: Gastroesophageal reflux disease (GERD) has become a major health problem globally, af... more Background: Gastroesophageal reflux disease (GERD) has become a major health problem globally, affecting patients' health-related quality of life (HRQOL). Barrett's esophagus (BE) is a precancerous lesion associated with GERD. BE patients might not only suffer from HRQOL losses by GERD but also face psychological distress due to the increased risk of developing cancer. However, the majority of patients in Asia have shorter BE segment which is different from the West. This study aimed to determine whether the HRQOL in BE patients were worse than in healthy referents in Taiwan. Methods: Patients who received referral esophagogastroduodenoscopy for various symptoms were evaluated for the existence of BE. Lesions were judged as endoscopically suspected esophageal metaplasia (ESEM) if they showed morphological resemblances to BE by endoscopy. The diagnosis of BE was confirmed by histology with intestinal metaplasia or gastric metaplasia based on the Montreal definition. The World Health Organization Quality of Life (WHOQOL-BREF) was administered to BE patients before treatment. For each BE patient, we selected 2 age-, sex-, educational background and municipality-matched healthy referents, sampled by simple randomization method from a national survey in Taiwan. Multiple linear regression models were constructed to control the potential confounders. Results: A total of 84 patients diagnosed with BE were enrolled as BE group and then compared with 168 healthy referents. The BE group had significantly lower WHOQOL-BREF scores than those of healthy referents in the physical domain (P < 0.05) but higher scores in the environment domain (P < 0.05). In the physical domain, the BE group had significantly lower scores in various facets, including pain, discomfort, sleep and rest and dependence on medications or treatments. There was no significant difference in social and psychological domains between the BE group and healthy referents. Conclusions: BE patients suffer from poor sleep and rest and high dependence on medications, which significantly reduce their quality of life. Individual facets of each domain warrants a better clinical healthcare to improve quality of life of BE patients.
PubMed, May 1, 2002
Mutant p53 protein and anti-p53 antibody in circulating blood can be detectedamong individuals wi... more Mutant p53 protein and anti-p53 antibody in circulating blood can be detectedamong individuals with mutations of the p53 tumor suppressor gene. Plasma mutant p53 protein and anti-p53 antibody have also been associated with vinyl chloride monomer (VCM) exposure, although the mechanism of VCM-related carcinogenesis remains unclear. Polymorphisms of metabolic and DNA repair genes have been implicated in chemical exposure-related carcinogenesis. The aim of this study is to explore the association between polymorphisms of metabolic and DNA repair genes with mutant p53 protein and anti-p53 antibody expression induced by VCM. Study subjects comprised 333 male workers occupationally exposed to VCM. Plasma mutant p53 protein and anti-p53 antibody detected with ELISA were grouped together as p53 overexpression. Genotypes of cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2), glutathione S-transferase T1 (GSTT1), and X-ray repair cross-complementing group 1 (XRCC1, exon 10) genes were identified by the PCR. High VCM exposure group had significantly higher p53 overexpression as compared with low exposure group [odds ratio (OR), 2.1; 95% confidence interval (CI), 1.1-3.8]. Individuals having experienced a high VCM exposure and displaying a XRCC1 Gln-Gln genotype had a highest risk of p53 overexpression among those having different combinations of VCM exposure and XRCC1 genotypes (OR, 6.5; 95% CI, 1.7-24.2). Interestingly, those subjects reflecting a CYP2E1 c2c2 genotype among the low VCM-exposure group demonstrated a greater risk of p53 overexpression (OR, 9.8; 95% CI, 1.2-81.6) as compared with those experiencing a low VCM exposure and CYP2E1 c1c1/c1c2 genotypes. Additional analysis revealed that individuals possessing more susceptible XRCC1 Gln-Gln, CYP2E1 c2c2, ALDH2 1-2/2-2, and non-null GSTT1 genotypes were more likely to reveal p53 overexpression. Our results suggest that susceptible XRCC1 and CYP2E1 genotypes may modulate the mutation of the p53 gene among VCM-exposed workers.
Toxicology Letters, May 1, 1995
Vinyl chloride monomer (VCM) is a suspected human carcinogen. Its metabolite, chloroethylene epox... more Vinyl chloride monomer (VCM) is a suspected human carcinogen. Its metabolite, chloroethylene epoxide, is able to alkylate the DNA molecule and to produce single strand breakage (SSB). A total of 244 workers from 4 polyvinyl chloride (PVC) manufacturing factories were recruited to assess the SSB of their peripheral lymphocyte DNA. The method of alkaline unwinding and hydroxyapatite chromatography was used to detect and calculate frequencies of SSB. In addition, h'epatitis B and C markers and the liver function of the workers were also examined. The worker's cumulative exposures to VCM were retrospectively constructed from the current monitoring data and each worker's job history. Multiple linear regression models were constructed to predict the worker's level of SSB and liver functions based on various exposure indices and variables, such as age, sex, smoking, drinking, and hepatitis markers. The results showed that current smoking and drinking status, and the presence of VCM exposures on the previous day were 3 major determinants of the level of SSB. Among the liver function tests, only y-glutamyl transpeptidase (GGT) was associated with current VCM exposures. In contrast, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were mainly affected by the presence of hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (anti-HCV). We conclude that GGT should be considered to be included in the regular health screening of VCM workers, and that the SSB method may not be suitable for long-term monitoring of cumulative exposure because of the quick DNA repair mechanism in humans. Keywor&: Single strand breakage (SSB); Peripheral lymphocyte; Alkaline unwinding and hydroxyapatite chromatography; Gamma glutamyl transpeptidase (GGT); Time-weighted average (TWA)
Journal of Occupational and Environmental Medicine, Jun 1, 2006
• Compare epidermal nerve density (END), estimated by immunohistochemical staining of skin biopsi... more • Compare epidermal nerve density (END), estimated by immunohistochemical staining of skin biopsies from the distal forearm, in ten men exposed occupationally to hand-transmitted vibrations and in age-and gendermatched control subjects. • Identify the results of sensory threshold testing and nerve conduction studies, and any correlations found between these or other factors on the one hand and END on the other. • Explain the implications of these findings for the development and early diagnosis of hand-arm vibration syndrome.
Toxicology, Sep 1, 2007
Although a relationship between vinyl chloride monomer (VCM) and liver cirrhosis has been reporte... more Although a relationship between vinyl chloride monomer (VCM) and liver cirrhosis has been reported, the underlying mechanisms are not clear. Cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2) and glutathione S-transferase theta 1 (GSTT1) enzymes are involved in activation and detoxification of VCM, and thus may be important determinants of interindividual susceptibility to VCM-induced liver damage, including liver cirrhosis. The objective of this study was to evaluate if metabolizing genetic polymorphisms could modify individual susceptibility to liver fibrosis of the VCM exposure. CYP2E1, ALDH2, and GSTT1 polymorphisms were determined by the PCR-RFLP method among 320 workers who were employed in five polyvinyl chloride manufacturing plants. Cumulative VCM exposure levels for study subjects were calculated using a job exposure matrix model. Thirteen workers were diagnosed as having liver fibrosis by using ultrasonography. We observed a dose-response trend between VCM exposure and liver fibrosis. Regarding the results on genetic polymorphisms, CYP2E1 c2c2 genotype showed a significant increase in the risk of liver fibrosis as compared to those with CYP2E1 c1c1 or c1c2 genotypes. No differences were observed between GSTT1 and ALDH2 genotypes and liver fibrosis. In summary, our result suggests that genetic polymorphism in CYP2E1 may be responsible for individual differences in susceptibility to liver fibrosis with regard to chronic VCM exposure. Thus, polymorphism analysis of metabolizing enzymes might be useful in the risk assessment of liver damage in workers with VCM exposure.
Journal of Occupational and Environmental Medicine, Sep 1, 2004
Occupational and Environmental Medicine, Jun 1, 1995
Objectives-To evaluate the effects of chronic exposure to lead on the peripheral nervous system i... more Objectives-To evaluate the effects of chronic exposure to lead on the peripheral nervous system in lead workers. Methods-Nerve conduction velocity and electromyographic studies were per- formed on 31 lead workers of a battery recycling factory and 31 sex and age matched controls. 25 cases with mild dis- tal extensor weakness of the upper limbs were classified as the lead neuropathy subgroup and the rest of the lead workers as the lead exposure subgroup. Blood lead concentrations and haematological and biochemical data were recorded. An index of cumulative exposure to lead was calculated by the summation of multiply- ing the average blood concentration of lead with the duration of exposure at various jobs. Results-Compared with the control group, the distal motor latency of the median nerve was significantly prolonged in the lead neuropathy subgroup, but not in the exposure subgroup. Only six of 31 workers had nerve conduction abnormalities, whereas electromyographic evi- dence of denervation was found in 93.5% of the lead neuropathy subgroup and 83-5% in the lead exposure subgroup. The electromyographic abnormalities found were neurogenic polyphasic waves in all 29 workers with abnormal electromyo- graphic findings (grade +++ in seven cases and grade ++ in the rest). Spontaneous activity was only recorded in seven workers, with grade + in four and grade ++ in three. There was a positive linear correlation between the index of cumulative exposure to lead and the distal motor latencies of the tibial nerve as well as a negative correlation with con- duction velocities of the sural nerve after multivariate analysis and control of potential confounding by age and sex. No correlation could be found between the electrophysiological values and a simple duration of exposure or concentration of blood lead. A non-parametric analysis showed that there was a trend of higher index of cumulative exposure to lead with more severe electromyographic changes. Electromyographic abnormality also occurred in workers with blood lead con- centrations between 17-4 and 58 ug/dI. Conclusion-Electromyographic study in the distal extensors of the upper limbs may be used as a tool for biological moni- toring of effect in lead workers.
Journal of Occupational and Environmental Medicine, Apr 1, 2003
• Identify previously reported findings relating occupational vinyl chloride monomer (VCM) exposu... more • Identify previously reported findings relating occupational vinyl chloride monomer (VCM) exposure to liver disease. • Relate how -and to what extent -hepatitis B surface antigen (HBsAg) status and particular job-related tasks interact to increase the risk of hepatocellular carcinoma in workers exposed to VCM. • Explain postulated mechanisms by which hepatitis B virus infection and VCM exposure may interact to cause liver cancer.
Quality of Life Research, May 24, 2008
Aims To compare the psychometric properties of the World Health Organization Quality of Life-BREF... more Aims To compare the psychometric properties of the World Health Organization Quality of Life-BREF (WHO-QOL-BREF) instrument and the St. George's Respiratory Questionnaire (SGRQ), and to examine the association between pulmonary function and domains and items of these questionnaires in patients with chronic obstructive pulmonary disease (COPD). Methods The WHOQOL-BREF and the SGRQ were administered to 211 patients. The reliability and validity of, and correlations among, the domain scores were examined. Multiple regression analyses were performed to identify which items were independently associated with subjects' lung functions. Results Both questionnaires showed good internal consistency (a [ 0.8), except the SGRQ symptoms domain (a = 0.66), minimal ceiling and floor effects, and good item convergent and item discriminant validity. There were moderate correlations between physical domain of the WHOQOL-BREF and activity, impacts and total domains of the SGRQ, and between psychological domain of the WHOQOL-BREF and impacts and total domains of the SGRQ. Eighteen items were significantly associated with lung function, particularly those items relating to mobility/ walking and activities of daily living (ADL). Conclusion Both the WHOQOL-BREF and the SGRQ showed comparable reliability and validity. Items related to mobility/walking and ADL may be useful in clinical screening for lung function impairment.
Occupational and Environmental Medicine, Aug 1, 1998
Objectives-Risk factors for increased blood lead concentration (BPb) has been investigated. Howev... more Objectives-Risk factors for increased blood lead concentration (BPb) has been investigated. However, the eVect of sibship and Chinese herbal medicine on BPb has not been systematically studied. In this study BPb data from voluntary testing was used to determine if Chinese herbal medicine and sibship were associated with BPb. Methods-319 children aged 1-7 were tested for BPb. Meanwhile, parents were interviewed to obtain information including consumption of Chinese herbal medicine, living environment, lifestyle, and sibship of the children tested. Results-The mean (SD) BPb of 319 preschool children was 4.4 (2.4) µg/dl. The consumption of Ba-baw-san (a Chinese herbal medicine) was significantly associated with increased BPb in children (p=0.038). Further multivariate regression analysis of BPb in 50 pairs of siblings showed the factors of being brothers explained 75% of variation for BPb, and being sisters and brother-sister explained 51% and 41% of variation respectively. Conclusion-Chinese herbal medicine and children's play patterns within the family expressed in diVerent types of sibship are the main determinants of low concentrations of BPb in preschool children of Taiwan.
Preventive medicine reports, Dec 1, 2016
This study estimates the annual numbers of eight work-related cancers, total losses of quality-ad... more This study estimates the annual numbers of eight work-related cancers, total losses of quality-adjusted life years (QALYs), and lifetime healthcare expenditures that possibly could be saved by improving occupational health in Taiwan. Three databases were interlinked: the Taiwan Cancer Registry, the National Mortality Registry, and the National Health Insurance Research Database. Annual numbers of work-related cancers were estimated based on attributable fractions (AFs) abstracted from a literature review. The survival functions for eight cancers were estimated and extrapolated to lifetime using a semi-parametric method. A convenience sample of 8846 measurements of patients' quality of life with EQ-5D was collected for utility values and multiplied by survival functions to estimate quality-adjusted life expectancies (QALEs). The loss-of-QALE was obtained by subtracting the QALE of cancer from age-and sex-matched referents simulated from national vital statistics. The lifetime healthcare expenditures were estimated by multiplying the survival probability with mean monthly costs paid by the National Health Insurance for cancer diagnosis and treatment and summing this for the expected lifetime. A total of 3010 males and 726 females with eight work-related cancers were estimated in 2010. Among them, lung cancer ranked first in terms of QALY loss, with an annual total loss-of-QALE of 28,463 QALYs and total lifetime healthcare expenditures of US$36.6 million. Successful prevention of eight work-related cancers would not only avoid the occurrence of 3736 cases of cancer, but would also save more than US$70 million in healthcare costs and 46,750 QALYs for the Taiwan society in 2010.
Cancer Detection and Prevention, 2003
Aims: To determine the presence of Asp13-p21-ki-ras oncoprotein and p53 oncoprotein in the plasma... more Aims: To determine the presence of Asp13-p21-ki-ras oncoprotein and p53 oncoprotein in the plasma of vinyl chloride monomer (VCM)-workers in Taiwan. Methods: We used enhanced chemiluminescence (ECL) western blotting to detect Asp13-p21-ki-ras and ELISA to detect mutant p53 protein (p53-Ag) and anti-p53 antibodies (p53-Ab) in the plasma of VCM-exposed workers. Results: Twenty-five out of 251 (10%) VCM-workers were positive for Asp13-p21-ki-ras in plasma, but 0 out of 36 controls were positive. There were 15 out of 95 (15.8%) plasma-positives among the more highly exposed (>480 ppm-month) workers and 10 out of 156 (6.4%) plasma-positives among the lesser exposed (≤480 ppm-month). Compared to the unexposed controls, age and drinking adjusted odds ratios (95% CI) were 1.2 (0.1, 9.8) in the lower exposed workers, and 4.8 (0.8, 28) in the higher exposed workers, and there was a significant linear trend between exposure and plasma positivity (P = 0.001). Thirty-three out of 251 (13.2%) VCM-workers were positive for the p53 over-expression (10% with positive p53-Ag and 2.8% with positive p53-Ab). There was a significant association between cumulative VCM exposure concentration and positive p53 expression (P = 0.032) among VCM-workers after adjusting for age, hepatitis, drinking and smoking status. Conclusions: Asp13-p21-ki-ras oncoprotein and p53 over-expression (p53-Ag or p53-Ab) can be found in the plasma of VCM-workers in Taiwan, and a significant dose-response relationship exists between plasma oncoproteins expression and VCM exposure.
Analysis of outpatient visits at a university hospital occupational and environmental clinic between 1987 and 1995
Chinese Journal of Public Health, 1999
Cluster Analysis of Environmental and Electromagnetic Field Health Risk Perception in Taiwan
Environmental health perspectives, Sep 13, 2011
P004 Recognition and compensation schemes for asbestos-related diseases (ards) in selected east asian countries
Introduction Asbestos products have been manufactured and consumed in large quantities in many Ea... more Introduction Asbestos products have been manufactured and consumed in large quantities in many East Asian countries over the past few decades. However, relatively few asbestos-related diseases (ARDs) have been recognised and compensated. This study compared the recognition and compensation schemes for ARDs in Japan, South Korea, Hong Kong and Taiwan. Methods Published materials were reviewed, followed with interviews with key informants. We first reviewed the conditions of asbestos exposures and compared the compensation statistics of ARDs across the studied regions. Secondly, we examined the legal frameworks for the recognition and compensation for ARDs, including the designs of compensation policies, sources of fund, eligibility for compensation, types of diseases and recognition criteria, and the scopes and levels of compensation benefits. Results In Japan, South Korea and Hong Kong, confirmed ARDs can be compensated regardless of claimants’ employment status, either through workers’ compensation insurance scheme or through compensation scheme under relief acts specifically designed for asbestos related health damages. In 2011, Japan, South Korea and Hong Kong compensated 1922, 632 and 18 ARD cases, respectively. In contrast, there have been very few ARDs being recognised in Taiwan (0 case in 2011), where compensation is restricted to workers with occupational asbestos exposure and thresholds for filing workers’ compensation are relatively high. Discussions Low recognition of ARDs can be attributed to biomedical factors, which involve the difficulties in making precise diagnosis, lack of information on previous exposure dose and duration, difficulties in establishing causality due to long disease latency and contamination from confounding exposures. Nevertheless, social factors are also important in determining how the social burden of occupational disease is negotiated. Among all, the design and function of workers’ compensation system, including policy frameworks and mechanisms for the recognition of occupational diseases, play an essential role.